For Patients

Symbyax (olanzapine and fluoxetine hydrochloride) is a combination medication used to treat depression caused by bipolar disorder (manic depression). It may also be used to treat depression when other medications have not worked. Symbyax is combines an atypical antipsychotic, olanzapine, which belongs to the thienobenzodiazepine class, and fluoxetine hydrochloride, which is a selective serotonin reuptake inhibitor. Common side effects include dizziness, drowsiness, diarrhea, dry mouth, constipation, increased appetite, weight gain, or trouble sleeping. Antidepressants can increase the risk of suicidal thoughts and behaviors. There may be an increased risk of serious or fatal side effects (e.g., stroke, heart failure) when used in elderly patients with dementia.

Symbax is taken once/day in the evening, in a 6-mg/25-mg capsule dose. Discuss with your doctor all medications you are taking as Symbax may interact adversely with many different drugs, including: MAO inhibitors, sibutramine, thioridazine, carbamazepine, cimetidine, phenytoin, drugs for anxiety, antipsychotics, antiarrhythmics, antidepressants, fosamprenavir/ritonavir, metoprolol, diuretics, aspirin, antiplatelet drugs, NSAIDs, blood thinners, drugs for high blood pressure, medicines for Parkinson's disease, drugs that increase serotonin, SSRIs, SNRIs, tryptophan, St. John's wort, amphetamines, alcohol, antihistamines, drugs for sleep, muscle relaxants, and narcotic pain relievers. During pregnancy, this medication should be used only when prescribed by a doctor. Babies born to mothers who have used this drug during the last 3 months of pregnancy may develop muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice these symptoms in your newborn, tell your doctor. This medication passes into breast milk and may have undesirable effects on a nursing infant. Breast-feeding is not recommended. Do not stop taking this medication without consulting your doctor. Some conditions may worsen when this drug is abruptly stopped.

Our Symbyax Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Get medical help right away if any of these rare but serious side effects occur: fainting, severe headache, seizures, eye pain/swelling/redness, vision changes (such as seeing rainbows around lights at night, blurred vision).

This drug may infrequently make your blood sugar level rise, an effect that may cause or worsen diabetes. This high blood sugar can rarely cause serious conditions such as diabetic coma. Tell your doctor immediately if you develop symptoms of high blood sugar, such as increased thirst/urination or unexplained weakness. If you already have diabetes, be sure to check your blood sugars regularly and share the results with your doctor. Your doctor may need to adjust your medication, diet, and exercise program when you start or stop this medication.

This drug may also cause significant weight gain and a rise in your blood cholesterol (or triglyceride) levels, especially in teenagers. These effects, along with diabetes, may increase your risk for developing heart disease. Discuss the risks and benefits of treatment with your doctor. (See also Notes section.)

This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.

This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, change in the amount of urine.

Olanzapine may rarely cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor immediately if you develop any unusual/uncontrolled movements (especially of the face/lips/tongue).

In rare cases, this medication may increase your blood level of a certain hormone (prolactin). For females, this rare increase in prolactin levels may result in unwanted breast milk, irregular/stopped menstrual periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.

For males, in the very unlikely event you have a painful or prolonged erection lasting 4 or more hours, stop using this drug and seek immediate medical attention, or permanent problems could occur.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

SIDE EFFECTS

Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect or predict the rates observed in practice.

Clinical Trials Experience

Adverse reactions were recorded by clinical investigators
using descriptive terminology of their own choosing. Consequently, it is not
possible to provide a meaningful estimate of the proportion of individuals
experiencing adverse reactions without first grouping similar types of
reactions into a limited (i.e., reduced) number of standardized reaction
categories.

In the tables and tabulations that follow, MedDRA or
COSTART Dictionary terminology has been used to classify reported adverse
reactions. The data in the tables represent the proportion of individuals who
experienced, at least once, a treatment-emergent adverse reaction of the type
listed. A reaction was considered treatment-emergent if it occurred for the
first time or worsened while receiving therapy following baseline evaluation.
It is possible that reactions reported during therapy were not necessarily
related to drug exposure.

The prescriber should be aware that the figures in the
tables and tabulations cannot be used to predict the incidence of side effects
in the course of usual medical practice where patient characteristics and other
factors differ from those that prevailed in the clinical studies. Similarly,
the cited frequencies cannot be compared with figures obtained from other
clinical investigations involving different treatments, uses, and
investigators. The cited figures, however, do provide the prescribing clinician
with some basis for estimating the relative contribution of drug and nondrug
factors to the side effect incidence rate in the population studied.

Adults

The information below is derived from a clinical study
database for SYMBYAX consisting of 2547 patients with treatment resistant
depression, depressive episodes associated with Bipolar I Disorder, Major
Depressive Disorder with psychosis, or sexual dysfunction with approximately
1085 patient-years of exposure. The conditions and duration of treatment with SYMBYAX
varied greatly and included (in overlapping categories) open-label and
double-blind phases of studies, inpatients and outpatients, fixed-dose and
dose-titration studies, and short-term or long-term exposure.

Adverse Reactions Associated with Discontinuation of
Treatment in Short-Term, Controlled Studies Including Depressive Episodes
Associated with Bipolar I Disorder and Treatment Resistant Depression

Overall, 11.3% of the 771 patients in the SYMBYAX group
discontinued due to adverse reactions compared with 4.4% of the 477 patients
for placebo. Adverse reactions leading to discontinuation associated with the
use of SYMBYAX (incidence of at least 1% for SYMBYAX and greater than that for
placebo) using MedDRA Dictionary coding were weight increased (2%) and sedation
(1%) versus placebo patients which had 0% incidence of weight increased and
sedation.

The most commonly observed adverse reactions associated
with the use of SYMBYAX (incidence ≥ 5% and at least twice that for
placebo in the SYMBYAX-controlled database) using MedDRA Dictionary coding
were: disturbance in attention, dry mouth, fatigue, hypersomnia, increased
appetite, peripheral edema, sedation, somnolence, tremor, vision blurred, and
weight increased. Adverse reactions reported in clinical trials of olanzapine
and fluoxetine in combination are generally consistent with treatment-emergent
adverse reactions during olanzapine or fluoxetine monotherapy.

Adverse Reactions Occurring at an Incidence of 2% or More
in Short-Term Controlled Studies Including Depressive Episodes Associated with
Bipolar I Disorder and Treatment Resistant Depression

Table 13 enumerates the treatment-emergent adverse
reactions associated with the use of SYMBYAX (incidence of at least 2% for
SYMBYAX and twice or more than for placebo). The SYMBYAX-controlled column
includes patients with various diagnoses while the placebo column includes only
patients with bipolar depression and major depression with psychotic features.

Extrapyramidal Symptoms

Dystonia, Class Effect for
Antipsychotics - Symptoms of dystonia, prolonged abnormal contractions of
muscle groups, may occur in susceptible individuals during the first few days
of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes
progressing to tightness of the throat, swallowing difficulty, difficulty
breathing, and/or protrusion of the tongue. While these symptoms can occur at
low doses, the frequency and severity are greater with high potency and at
higher doses of first generation antipsychotic drugs. In general, an elevated
risk of acute dystonia may be observed in males and younger age groups
receiving antipsychotics; however, events of dystonia have been reported
infrequently ( < 1%) with the olanzapine and fluoxetine combination.

Additional Findings Observed in
Clinical Studies

Sexual Dysfunction - In the pool of
controlled SYMBYAX studies in patients with bipolar depression, there were
higher rates of the treatment-emergent adverse reactions decreased libido,
anorgasmia, erectile dysfunction and abnormal ejaculation in the SYMBYAX group
than in the placebo group. One case of decreased libido led to discontinuation
in the SYMBYAX group. In the controlled studies that contained a fluoxetine
arm, the rates of decreased libido and abnormal ejaculation in the SYMBYAX
group were less than the rates in the fluoxetine group. None of the differences
were statistically significant.

Sexual dysfunction, including
priapism, has been reported with all SSRIs. While it is difficult to know the
precise risk of sexual dysfunction associated with the use of SSRIs, physicians
should routinely inquire about such possible side effects.

There are no adequate and
well-controlled studies examining sexual dysfunction with SYMBYAX or fluoxetine
treatment. Symptoms of sexual dysfunction occasionally persist after
discontinuation of fluoxetine treatment.

Difference Among Dose Levels
Observed in Other Olanzapine Clinical Trials

Other Adverse Reactions
Observed in Clinical Studies

Following is a list of
treatment-emergent adverse reactions reported by patients treated with SYMBYAX
in clinical trials. This listing is not intended to include reactions (1)
already listed in previous tables or elsewhere in labeling, (2) for which a
drug cause was remote, (3) which were so general as to be uninformative, (4)
which were not considered to have significant clinical implications, or (5)
which occurred at a rate equal to or less than placebo.

Reactions are classified by
body system using the following definitions: frequent adverse reactions are
those occurring in at least 1/100 patients; infrequent adverse reactions are
those occurring in 1/100 to 1/1000 patients; and rare reactions are those occurring
in fewer than 1/1000 patients.

Children and Adolescent Patients (aged 10 to 17 years)
with a Diagnosis of Bipolar Depression

The information below is derived from a single, 8-week,
randomized, placebo-controlled clinical trial investigating SYMBYAX for the
treatment of bipolar I depression in patients 10 to 17 years of age.

Adverse Reactions Associated with Discontinuation of
Treatment in the single pediatric study

Overall, 14.1% of the 170 patients in
the SYMBYAX group discontinued due to adverse reactions compared with 5.9% of
the 85 patients for placebo. Adverse reactions leading to discontinuation
associated with the use of SYMBYAX (incidence of at least 1% for SYMBYAX and
greater than that for placebo) using MedDRA Dictionary coding were weight
increased (2.9%), suicidal ideation (1.8%), bipolar disorder (1.2%), and somnolence
(1.2%) versus placebo patients which had 0% incidence of weight increased,
bipolar disorder, and somnolence, and a 1.2% incidence of suicidal ideation.

Adverse Reactions Occurring at an Incidence of 2% or more
and greater than placebo - Table 14 enumerates the treatment-emergent adverse
reactions associated with the use of SYMBYAX (incidence of at least 2% for
SYMBYAX and twice or more than for placebo).

As with olanzapine, asymptomatic elevations of hepatic
aminotransferases [ALT, AST, and GGT] and alkaline phosphatase have been
observed with SYMBYAX. In the SYMBYAX-controlled database, clinically
significant ALT elevations (change from < 3 times the upper limit of normal
[ULN] at baseline to ≥ 3 times ULN) were observed in 5% (38/698) of
patients exposed to SYMBYAX compared with 0.5% (2/378) of placebo-treated
patients and 4% (33/751) of olanzapine-treated patients. ALT elevations
≥ 5 times ULN were observed in 2% (11/701) of SYMBYAX-treated patients,
compared to 0.3% (1/379) of placebo-treated patients and 1% (11/760) of
olanzapine-treated patients. No patient with elevated ALT values experienced
jaundice or liver failure, or met the criteria for Hy's Rule. ALT values
returned to normal, or were decreasing, at last follow-up in the majority of
patients who either continued treatment with SYMBYAX or discontinued SYMBYAX.

Rare postmarketing reports of hepatitis have been
received in patients treated with olanzapine. Very rare cases of cholestatic or
mixed liver injury have also been reported in the postmarketing period in
patients treated with olanzapine.

Caution should be exercised in patients with signs and
symptoms of hepatic impairment, in patients with preexisting conditions
associated with limited hepatic functional reserve, and in patients who are
being treated with potentially hepatotoxic drugs.

An increase in creatine phosphokinase has been reported
very rarely in SYMBYAX-treated patients and infrequently in clinical trials of
olanzapine-treated patients.

QT Interval Prolongation - The mean increase in QTc
interval for SYMBYAX-treated patients (4.4 msec) in clinical studies was
significantly greater than that for placebo-treated (-0.8 msec),
olanzapine-treated (-0.3 msec) patients, and fluoxetine-treated (1.7 msec)
patients. There were no significant differences between patients treated with
SYMBYAX, placebo, olanzapine, or fluoxetine in the incidence of QTc outliers
( > 500 msec).

Children and Adolescents (aged 10 -17 years)

In a single 8-week randomized, placebo-controlled
clinical trial investigating SYMBYAX for treatment of bipolar I depression in
patients 10 to 17 years of age, the following was observed:

Vital Signs - In the SYMBYAX-treated patients
compared with placebo-treated patients, the mean orthostatic blood pressure and
standing pulse rate were not significantly different between treatment groups.

Body Weight: An increase in weight greater than or
equal to 7% occurred in 52.4% of the SYMBYAX group and 3.6% of the placebo
group. Weight gain greater than or equal to 15% occurred in 14.1% of the
SYMBYAX group and none of the placebo group.

Postmarketing Experience

The following adverse reactions have been identified
during post-approval use of SYMBYAX. Because these reactions are reported
voluntarily from a population of uncertain size, it is difficult to reliably estimate
their frequency or evaluate a causal relationship to drug exposure.